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• W2892423237 abstract "Over the last decades, significant advances in targeted therapies have helped provide more effective treatment for head and neck cancer patients. However, chemo-resistance to cisplatin significantly contributes to treatment failure in the clinical management of patients. In response to chemotherapeutic agents, certain molecules inside the cell are released or secreted from damaged or dead/dying cells, named damage-associated molecular patterns (DAMPs), thereby initiating an immune response through interaction with pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs). In present study, we investigated the link between cisplatin-induced DAMPs and TLR3 signaling. We found that cisplatin could be a potential activator of TLR3 and cisplatin treatment results in activation of PRRs' signaling and down-stream associated cytokine/chemokine, IFNβ, and CCL5 in TLR3High OC2 cells, but not in TLR3Low FaDu cells. Furthermore, knockdown of the TLR3 gene attenuates the expression of IFNβ and CCL5 mRNA and enhances the cytotoxicity of cisplatin in TLR3High OC2 cells. To determine whether TLR3 status affects the stress response of OC2 cells to cisplatin, we generated TLR3 knockdown OC2 cells (psi-TLR3 cells) with a psiRNA-hTLR3 plasmid containing shRNA to TLR3 and control OC2 cells (psi-NT cells) expressing non-silencing shRNA. OC2 cells were more sensitive to cisplatin treatment after TLR3 knockdown. In our animal model, OC2 psi-NT cells were more tumorigenic than were OC2 psi-TLR3 cells. Together, our in vitro and in vivo data imply TLR3 may contribute to tumor development and protect cisplatin-induced DNA damage response leading to cisplatin resistance in head and neck cancer cells." @default.
• W2892423237 created "2018-10-05" @default.
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• W2892423237 date "2018-11-01" @default.
• W2892423237 modified "2023-10-16" @default.
• W2892423237 title "Triggering TLR3 pathway promotes tumor growth and cisplatin resistance in head and neck cancer cells" @default.
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• W2892423237 doi "https://doi.org/10.1016/j.oraloncology.2018.09.015" @default.
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